› 7rt5

X-ray diffraction
1.29Å resolution

Crystal structure of KRAS G12D with compound 36 (4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-7-(8-ethynyl-7-fluoronaphthalen-1-yl)-8-fluoro-2-{[(4s,7as)-tetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy}pyrido[4,3-d]pyrimidine) bound

Released:
DOI: 10.2210/pdb7rt5/pdb
PDB entry 7rt5 coloured by chain, front view.
PDB entry 7rt5 coloured by chain, side view.
PDB entry 7rt5 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Identification of MRTX1133, a Noncovalent, Potent, and Selective KRASG12D Inhibitor.
Wang X, Allen S, Blake JF, Bowcut V, Briere DM, Calinisan A, Dahlke JR, Fell JB, Fischer JP, Gunn RJ, Hallin J, Laguer J, Lawson JD, Medwid J, Newhouse B, Nguyen P, O'Leary JM, Olson P, Pajk S, Rahbaek L, Rodriguez M, Smith CR, Tang TP, Thomas NC, Vanderpool D, Vigers GP, Christensen JG, Marx MA
J Med Chem 65 3123-3133 (2022)
PMID: 34889605

Function and Biology Details

Reaction catalysed: 
GTP + H(2)O = GDP + phosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-133991 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
GTPase KRas, N-terminally processed Chain: A
Molecule details ›
Chain: A
Length: 170 amino acids
Theoretical weight: 19.36 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P01116 (Residues: 1-169; Coverage: 89%)
Gene names: KRAS, KRAS2, RASK2
Sequence domains: Ras family

Ligands and Environments

3 bound ligands:
Ligand GDP 1 x GDP
Ligand 7OE 1 x 7OE
Ligand MG 1 x MG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 24-ID-E
Spacegroup: P212121
Unit cell:
a: 39.865Å b: 51.935Å c: 88.658Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.164 0.162 0.187
Expression system: Escherichia coli

Quick links

Citations

60 review citations

Pancreatic Cancer: Pathogenesis, Screening, Diagnosis, and Treatment.
Wood et al. (2022)
59 more

1 mention without citation

In Silico Evaluation of the Thr58-Associated Conserved Water with KRAS Switch-II Pocket Binders.
Leini et al. (2023)